Implementation of a Prevention Bundle to Decrease Rates of Staphylococcus aureus Surgical Site Infection at 11 Veterans Affairs Hospitals

Key Points Question Is a surgical site infection (SSI) prevention bundle with facility-level discretion on its components associated with decreased Staphylococcus aureus deep incisional or organ space SSI after cardiac surgery or total joint arthroplasty? Findings In this quality improvement study that implemented an SSI prevention bundle at 11 Veterans Affairs hospitals and included 23 005 surgical procedures, there was a significant association between the intervention and decreased deep incisional or organ space SSI rates among patients undergoing total joint arthroplasty but not among those undergoing cardiac surgery analyzed with a multivariable logistic regression model. The association was not observed when analyzed with an interrupted time-series model. Meaning The findings of this study suggest that implementation of an SSI prevention bundle with facility-level discretion on its components may be associated with decreased deep incisional or organ space S aureus SSI after total joint arthroplasty, but further research is needed to investigate this association outside of randomized trial settings.


Introduction
Surgical site infections (SSIs) are associated with significant morbidity and mortality, prolonged length of hospital stay, and readmission. 1 Staphylococcus aureus is the most common etiology of adult SSIs, and specifically the most common pathogen causing SSIs among orthopedic (38.6%) and cardiac (27.0%) surgery patients. 2 S aureus nasal carriage is an important risk factor for SSI after cardiac and orthopedic surgery. [3][4][5] Studies have found that the majority of patients who develop SSIs with S aureus carry a genetically identical strain in their nares. 4,6 A multicenter study involving 20 hospitals in the United States (STOP SSI study) found that implementation of an SSI prevention bundle decreased rates of deep incisional or organ space S aureus SSI by 42% among patients undergoing cardiac and orthopedic surgery. 7 The bundle used in that study included chlorhexidine gluconate (CHG) bathing, S aureus nasal screening, nasal mupirocin decolonization for S aureus carriers, and perioperative antibiotic prophylaxis based on whether the patient was a methicillin-resistant S aureus (MRSA) carrier. However, it is well known that interventions are not one-size-fits-all and may need to be modified to address facility-level factors, such as laboratory capacity, and other barriers to implementation. 8 Our prior research on this SSI prevention bundle found that barriers to bundle implementation could be overcome by adapting and tailoring strategies to stakeholders and settings. 9 The aim of this quality improvement study was to implement an SSI prevention bundle while allowing for discretionary implementation of specific component interventions among 11 Veterans Affairs (VA) medical centers to assess the change in S aureus SSI rates when the prevention bundle was implemented outside a strict randomized clinical trial setting.

Ethics
This study was approved by the VA Central institutional review board as well as the Research and Development Committees of each participating hospital. It was preregistered on ClinicalTrials.gov (NCT02216227). This study was conducted using routinely collected data without direct patient contact and was deemed of minimal risk. A waiver of informed consent was obtained. We followed the SQUIRE Standards for Quality Improvement Reporting Excellence 2.0 (SQUIRE) guidelines for reporting. 10

Study Design and Patient Population
We conducted a quasi-experimental before-and-after study of all patients who underwent 1 of 3 primary surgical procedures: coronary artery bypass grafting (CABG), cardiac valve replacement, or total joint arthroplasty (TJA, which indicates total hip arthroplasty or total knee arthroplasty) at 11 VA medical centers. Before bundle implementation, SSI prevention efforts such as S aureus screening, CHG bathing, or perioperative antibiotic prophylaxis were not standardized.

Intervention
The project held an in-person kickoff meeting to review project aims. Throughout the project, investigators and coordinators from all sites attended twice monthly conference calls to discuss local and national barriers and facilitators. All sites were given facilitation tools, such as information sheets,

Outcomes
The primary outcome of interest was deep incisional or organ space SSI caused by S aureus within 90 days after index surgery. Organ space SSI included mediastinitis, endocarditis, and prosthetic joint infection. SSI was defined using the VA Surgical Quality Improvement Program (VASQIP) data collected monthly by experienced nurse data managers. 11 VASQIP covers approximately 70% of operative cases, thus we assessed cases outside the VASQIP sample using a previously described fully automated SSI detection algorithm. 12 That algorithm was also used to assess SSIs outside the 30-day follow-up period used by the VASQIP program.

Statistical Analysis
Numbers of deep incisional or organ space S aureus SSI were summarized as frequencies and percentages for the preintervention period and the postintervention period. The χ 2 test was used to compare the frequency of deep incisional or organ space S aureus SSI between the 2 periods. A patient-level multivariate generalized estimating equation (GEE) model with a logit link and robust SEs clustered within site was assessed. Odds ratios (ORs) and 95% CIs were reported. Similar models were applied to the outcome MRSA SSI.
Although we were not statistically powered to see a significant difference, we performed additional sensitivity analyses. First, we assessed the association between the intervention and deep incisional or organ space SSI among hospitals that screened for both MRSA and MSSA or hospitals that screened for only MRSA. Then an interrupted time-series (ITS) model was fit to account for baseline trends, autocorrelation, and time trends before and after the intervention implementation using a generalized linear model with a negative binomial distribution, log link function, and fixed site effects. Incidence rate ratio (IRR) and 95% CIs were reported.
All statistical tests were 2-sided, and statistical significance was defined as α < .05. Analyses were conducted using SAS version 9.4 software (SAS Institution).

Results
In total, 23 005 surgical procedures (6696 cardiac operations and 16 309 TJAs) were included in this study ( Table 2). All 11 hospitals implemented the intervention among patients who underwent TJA.
Six hospitals implemented the intervention among patients who underwent cardiac surgery. Hospital D did not perform cardiac surgery but implemented S aureus testing and decolonization among patients sent to hospital E for cardiac surgery. The timing of implementation and specifics on how each hospital implemented the infection prevention bundle are summarized in Table 2. Six hospitals hospitals reported an increased proportion of SSIs, and 1 hospital did not experience mediastinitis or endocarditis in either period (Figure). In the GEE model adjusting for hospital-level correlation, there    (Figure). In the GEE model adjusting for hospital-level correlation, we found a statistically significant association between the intervention and decreased deep incisional or organ space S aureus SSI among patients undergoing TJA (adjusted OR, 0.55; 95% CI, 0.31-0.98). We performed a post hoc power analysis to determine the power necessary to reject the null hypothesis of no difference in deep incisional or organ space S aureus SSI, based on our results. We found that our analysis had 50% power to reject the null hypothesis of no difference.

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We then evaluated the association of the intervention with deep incisional or organ space SSI

Sensitivity Analyses
We evaluated the difference in the association between the intervention and deep incisional or organ

Discussion
This multicenter study evaluated the association between an SSI prevention bundle with facility-level discretion on its various components and S aureus deep incisional or organ space SSI rates. While we found a statistically significant difference among patients after TJA via GEE analysis, the association was not observed in the ITS analysis. In contrast, there was not a statistically significant association among patient after cardiac operations in either analysis.
Although both the GEE and ITS analyses were underpowered, post hoc power for the GEE and ITS models among patients after TJA were 50% and 21%, respectively. The lack of power in the ITS analysis was most likely derived from the rarity of the deep incisional or organ space SSI in each time point.
Our results corroborate the findings of the STOP SSI study, which evaluated a similar bundled intervention at 20 hospitals in Hospital Corporation of America-affiliated hospitals. The STOP SSI study used a well-defined bundle. Therefore, the focus was to show internal validity and to isolate the outcomes of the bundle from all external influences. 7,13,14 In contrast, our study was an effectiveness study, in which we allowed much more flexibility in the choice of chlorhexidine bathing products, the method for screening of S aureus, and the use of mupirocin or povidone-iodine for decolonization.

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Our study not only assessed internal validity but also considered external validity in various clinical settings. 14 In contrast to possible lower SSI rates after TJA, we did not observe changes in SSI rates after cardiac operations. This is in line with the STOP SSI study but discordant with a previous randomized clinical trial, 6 which showed S aureus nasal screening and decolonization significantly decreased SSI rates after cardiac operations. The lack of an association among patients undergoing cardiac surgery is likely due to barriers to bundle adherence. While TJAs are usually performed as a nonemergent procedure, cardiac surgery, such as CABG surgery, often needs to be performed urgently. In our study, it was very difficult to implement the intervention among patients undergoing cardiac surgery, who unlike those undergoing orthopedic surgery, do not have routine preoperative clinic visits prior to surgery.
In the sensitivity analyses that evaluated the association between the intervention and SSI rates at hospitals that screened for both MRSA/MSSA nasal carriage and hospitals that screened for only MRSA, we found similar results although the associations were not statistically significant, with wide confidence intervals. This is likely due to the smaller number of outcomes in this subgroup. A previous meta-analysis suggested S aureus decolonization and bundled approaches were associated with lower rates of both MSSA SSI and MRSA SSI. 15 The same meta-analysis found use of glycopeptides, such as vancomycin, as a perioperative antibiotic was protective against MRSA SSIs but not for MSSA SSIs. Several other studies reported that perioperative use of vancomycin was associated with higher rates of overall SSI compared with perioperative use of cefazolin. 16,17 Based on the best existing data, a targeted bundled approach with S aureus screening, nasal decolonization, and use of the most appropriate perioperative antibiotic based on screening result (cefazolin for MSSA and vancomycin plus cefazolin for MRSA) may be the optimal strategy to decrease S aureus SSI, in combination with CHG bathing.

Limitations
There are limitations in our study. First, we were unable to assess adherence because CHG was not always dispensed through pharmacy and because of variation in facility-level documentation of patient use of CHG and mupirocin at home. However, a survey at hospital D found that among TJA patients, 85% of patients were adherent to CHG bathing and 53% were adherent to mupirocin as directed. 18 Similarly, we were unable to assess how thoroughly the intervention was implemented at each hospital. Qualitative interviews with health care workers at 3 of these hospitals found that facility-level adherence to the bundle varied due to barriers and facilitators, such as presence of a champion and level of buy-in among local staff. 9 In addition, we did not have patient-level information to know whether the patients who developed an SSI received all appropriate components of the bundled intervention. All these limitations make it difficult to assess whether changes in SSI rates were attributable to the bundled intervention. Second, deep incisional or organ space S aureus SSIs are very rare events, so the study was underpowered to adjust for important confounding variables. This limitation undermines our ability to provide strong evidence for an association between the intervention and a decrease in deep incisional or organ space S aureus SSIs, even among patients undergoing TJA, because we were unable to statistically adjust for important confounders. The ITS analysis did not show a statistically significant difference for patients undergoing TJA although the incidence rate ratio was still less than 1. Third, we used the fully automated SSI detection algorithm for approximately 30% of cases outside the sample followed by VASQIP. Although the SSI detection algorithm was associated with moderate positive predictive values (52.5% for cardiac operations and 83.3% for TJAs) and high negative predictive values (99.8% for cardiac operations and 99.4% for TJAs), there was a possibility of ascertainment bias. However, the SSI rates were similar when assessed by VASQIP nurse managers and the automated SSI detection algorithm. Thus, we believe there is little concern for ascertainment bias. Additionally, our study was conducted within the Veterans Health Administration system where most patients were